Discovery of Lead Compounds - Introduction

Question 1

What is a lead compound?

Answer 1

A chemical compound with pharmacological or biological activity that serves as a starting point for drug development. It undergoes chemical modifications to improve parameters (e.g., potency, safety, bioavailability).

Question 2

Why are lead compounds economically valuable?

Answer 2

• Potential financial assets due to high therapeutic and market value.
• Can lead to breakthrough drugs.

Question 3

What are the primary sources of lead compounds?

Answer 3

1. Natural products (plants, bacteria, fungi, marine organisms).
2. Libraries of synthesized compounds (CombiChem, FBDD).
3. High-Throughput Screening (HTS).
4. Rational Drug Design.
5. Structure-Based Drug Design (SBDD).

Question 4

Provide examples of drugs derived from natural products.

Answer 4

• Warfarin (anticoagulant).
• Paclitaxel (anticancer).
• Morphine (analgesic).
• Artemether (antiparasitic).

Question 5

What is the significance of Vicriviroc as a lead compound?

Answer 5

• Developed as a CCR5 antagonist for HIV therapy.
• Improved selectivity for CCR5 receptors.
• Reduced hERG ion channel affinity to enhance safety.

Question 6

What are sulfonamides, and why are they significant?

Answer 6

• First antibacterial agents.
• Derived drugs include Furosemide (diuretic), Carbutamide (hypoglycemic), Acetazolamide (carbonic anhydrase inhibitor).

Question 7

Describe the pharmacological action of morphine.

Answer 7

• µ-opioid receptor agonist.
• Effects: Analgesia, euphoria.
• Side effects: Respiratory depression, constipation.

Question 8

How has cocaine influenced drug development?

Answer 8

• Originally used as a local anesthetic.
• Limitations: Cardiotoxicity, abuse potential.
• Inspired development of simpler anesthetics like procaine.

Question 9

What are psychedelics, and how are they used in mental health?

Answer 9

• Alter sensory perception, treat depression, PTSD.
• Examples: Psilocybin (5-HT2A agonism), LSD.

Question 10

What are the key challenges in drug discovery?

Answer 10

• Balancing efficacy, safety, and affordability.
• Reducing development time.
• Overcoming drug resistance (e.g., antibiotics).

Question 11

What is high-throughput screening (HTS)?

Answer 11

Rapidly testing thousands of compounds for biological activity.

Question 12

What are “me-too drugs”?

Answer 12

Drugs structurally similar to existing drugs, improving properties of the original drug (e.g., statins).

Question 13

What is the role of serendipity in drug discovery?

Answer 13

Accidental discoveries of lead compounds (e.g., penicillin, LSD).

Question 14

How has cannabis contributed to medicine?

Answer 14

THC and CBD used in drugs like Epidyolex (epilepsy), Nabiximols (MS spasticity), and Nabilone (antiemetic).

Question 15

What are examples of natural sources for drugs?

Answer 15

• Plants (e.g., morphine).
• Bacteria (e.g., Streptomyces-derived antibiotics).
• Fungi (e.g., penicillin).